Chen C.-S.Lin S.-T.2019-05-092019-05-0920168885885https://scholars.lib.ntu.edu.tw/handle/123456789/406869The octanol-water partition coefficient (KOW) is a measure of the relative hydrophobicity and hydrophilicity of a chemical. Knowledge regarding how this value changes with the acidity (pH value) in the aqueous phase is important for understanding many biological activities. In this work, we develop a computational method to predict the effect of pH on the partition coefficient of ionizable drugs. In particular, three dissociation mechanisms were examined based on four relevant properties: the acid dissociation constant (pKa), and the octanol-water partition coefficient of the molecule in the neutral form (KOW,N), in the form of free ions (KOW,I) and in the form of an ion pair (KOW,IP). The values of KOW,N, KOW,I, and KOW,IP are predicted based on the COSMO-SAC activity coefficient model, and the value of pKa is determined using the SMD solvation model. The root-mean-square (RMS) error in the predicted log KOW,N, log KOW,IP, and pKa for 41 pharmaceuticals are found to be 0.636, 0.816, and 2.59, respectively. The predicted overall partition coefficient, as a function of pH, is also compared to experimental values whenever available. Our results show that the proposed method can provide satisfactory a priori prediction of pH dependency of KOW without input of any experimental data. This method can serve as a useful tool for modern drug delivery. ? 2016 American Chemical Society.journal article10.1021/acs.iecr.6b020402-s2.0-84984682108https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984682108&doi=10.1021%2facs.iecr.6b02040&partnerID=40&md5=084dfe73f768b1015e30fe6c1872cede